BEE VENOM TREATMENT FOR OVARIAN CANCER
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The female reproductive gland is known as an ovary and as there are two glands present hence, they are known as ovaries. Ovaries are responsible for producing eggs and female hormones like progesterone and estrogen. Ovarian cancer surfaces when the abnormal cells located in ovaries start multiplying and their production gets out of control. It eventually leads to a tumor. Ovarian cancer is also a collective name given to multiple cancers that originate from, in and around the ovaries.
What are the types of ovarian cancer? Most of the cases of ovarian cancer are reported to occur in women aged between 60 to 70 years old. This type of cancer is divided into two different categories: epithelial cancer and non-epithelial cancer. |
Cancer that grows in the fallopian tube, the peritoneum and the outer surface of the ovary is called epithelial cancer. While cancer that originates from the inside of an ovary is called non-epithelial cancer. There is another type of tumor called borderline tumor, it exists between the benign and malignant borderline. This tumor results due to changes occurring in the number of cells, but it is not called cancer.
What are the reasons that cause ovarian cancer?
Ovarian cancer is caused due to different risk factors that are associated with: multiple ovulation periods, few pregnancies, infertility, late menopause, and early menopause. In the same manner, different natural factors protect from ovarian cancer like having several pregnancies, making proper use of contraceptives, breastfeeding and undergoing sterilization or ovarian removal. Lifestyle factors like having a normal BMI index and an active lifestyle also helps in getting rid of the risk of catching ovarian cancer. There are also hereditary variants that lead to ovarian cancer.
Elaborating further, BRCA1 and BRCA2 mutation most commonly develops a risk for women to become a victim of ovarian cancer or breast cancer. On the other hand, inherited mutations, which have any sort of link to other forms of cancer, in both women and men, can also indicate an increased risk of catching ovarian cancer. It is to be noted that most of the women, who are more than 50 years of age are diagnosed with this type of cancer.
Anticancer Activity of Toxins from Bee and Snake Venom—An Overview on Ovarian Cancer
Cancer is one of the most problematic diseases when it comes to a public health concern. Angiogenesis is an abnormal proliferation of tumor responsible cells and there is a complex relationship between different cancer cells and components of the extracellular matrix, which can be regarded as an important development of the phase of carcinogenesis. This pathway of this action is being examined to develop an effective anti-cancer treatment.
According to different clinical studies, it has been found that toxins contained in different types of venoms generate an anti-cancer effect on the human cancer cell threads. This provides a new prospect in the field of developing anti-cancer drugs.
In this study, the effect of natural toxins contained in snake and bee venom was scrutinized under a special therapy regime to understand their mechanism that prevents the proliferation and growth of cancer cells. During this research, various molecules were studied from the venom source that can contain ovarian cells that lead to ovarian cancer. It was found that especially bee venom contains several helpful toxins that can pave a way for developing a safe anti-cancer therapy that could be followed instead of conventional chemotherapy that has several dangerous side effects.
This study can help improve the effectiveness of the standard anti-cancer therapies and also regulate a proper dose of chemotherapy that could be less dangerous for the patients of ovarian cancer. Such types of studies, which rely on using natural sources, for treating the gravest diseases and illnesses are immediately required to bring some relief for the patients suffering from different types of cancers. These studies, carried out in-depth, also help explore the molecular mechanism of toxins on the cancer cells.
Bee venom activity
Bee venom contains different active compounds that possess pharmaceutical activities. Most useful are the carbohydrates (non-peptic compounds) and peptides that include adolapin and apamin, MCD (mast cell de-granulating peptide, melittin, phospholipase A2 (enzymes) and biogenic amines (norepinephrine, dopamine, and histamine). Most of the clinical studies are conducted to explore the effect of these bee venom compounds that carry the biological activity.
Through Melittin
Melittin is regarded as the main element of bee venom. It is a complex protein that has 26 amino acid residues. It can be easily dissolved in water and it also has been found that it disrupts and integrates the phospholipid bilayers (synthetic and natural). In the view of different reports, it can be deduced that melittin certainly delivers different effects like anti-viral, anti-inflammatory, anti-bacterial properties and prevent the progression of malignant cells, apoptosis, and cell cycle arrest.
Through Apamin
Apamin is the second most important element of bee venom and it has 10 amino acids that have two disulfide bonds. It is also known as the smallest existing neurotoxin in BV. Apamin’s main effect is; categorized inhibition of the Ca2+ activated K+ channels. What an apamin does is that it blocks all the channels through minimum concentration and enhances neuronal excitability and plasticity.
According to a scholarly research article, Ichii et al, it was reported that apamin effects tracheal contraction by releasing histamine from the lung tissues and that ultimately helps in decreasing allergic inflammation of the airway. A study conducted in 2003, showed that apamin also prevents nitric oxide generated relaxation of myometrium in expecting mothers.
Through MCD
MCD is another important compound that contains 22 amino acids and carries 2 disulfide bonds between the Cys5, 19 and Cys3, 15. MCD prevents the production of histamine from the mast cells under minimum concentrations carrying the anti-allergic activity. Studies reveal that this process of inhibition of histamine is fairly possible when the concentration administered is in a larger volume than the naturally released quantity of histamine. The reason is that it comes in action with the immunoglobulin E-molecule.
Through Adolapin
There is another useful peptide, called adolapin that carries analgesic, antipyretic and anti-inflammatory properties and also prevents the activity of bee venom phospholipase A2. Adolapin carries this trait because; it inhibits the prostaglandin synthesis process by cyclooxygenase inhibitory characteristics.
Effect of Bee Venom on Cancer Cells
Through its different mechanisms, bee venom induces apoptosis of the malignant cells and prevents the growth of the tumor. Phospholipase A2 activation with the help of melittin is generally regarded as the most crucial mechanism of bee venom. According to Gajski, it was recorded that melittin certainly has inhibitory effects on calmodulin as an anti-proliferation agent of BV. It also leads to an enhanced PLA2 activity, necrosis and calcium influx.
A study concluded that general activity of bee venom on different types of cancer-causing cells is carried out by compounds that induce apoptosis through activation of caspase-3 and caspase-9 or by releasing AIF and EndoG from mitochondria. Researchers, belonging to this study, also investigated in detail the molecular mechanism of bee venom that induces apoptosis in the human bladder cancer cells. It was found that there are different pathways like promoting activation of initiating effector-caspase and caspases with the Fas/CD95 (adaptor proteins), inducing the release of the reactive oxygen species and the ER and Ca2+ stress-mediated apoptotic death and behaving as a receptor for the bee venom.
A study was conducted in 2010, regarding lung cancer that determined that various compounds of BV carry anti-angiogenic effects, as they block the tyrosine phosphorylation of VEGFR2. In this study, the molecular mechanism of melittin, in link with its pharmacological activity, was also observed in the leukemic U937 cells. It was concluded that bee venom generates down-regulation of Akt and ERK signal pathways by caspase-3 and Bcl-2 acting as the main regulators that induce apoptosis.
A study carried out in 2012, examined thoroughly the cytotoxic effect of BV in combination with the cisplatin on cisplatin-resistant cancer cells (A2780cp cells). Treatment was carried out by administering 8µ/mL of BV or 25mg/mL of cisplatin for nearly 24 hours that resulted in the death of cisplatin-resistant cancer cells by 50%.
A simultaneous treatment also delivered the same results, where cisplatin was maintained at 10mg/mL and bee venom was administered at 4µg/mL for nearly 24 hours. The researchers investigated the effect on the expression of Bcl2 that showed a decrease in the cisplatin-resistant cancer cells after the cells were subjected to cisplatin and bee venom.
This study concluded that bee venom has a positive effect on ovarian cancer cells and also enhanced the cytotoxic effect on cisplatin, which is an anti-tumor agent.
According to another study carried out in 2015, the pro-apoptotic and cytotoxic effect of chrysin and bee venom was examined on the cisplatin-resistant ovarian cancer cells. For the clinical study, chrysin was given at 40µg/mL and bee venom at 8µg/mL while, a combination of chrysin and bee venom at 15µg/mL and 6µg/mL respectively, resulted in the death of cisplatin-resistant ovarian cancer cells by 50%.
The study done above is by Alizedehnohi et al. carried out about the downregulation of Bcl-2. Researchers of this study established that there is a special mechanism through which chrysin and bee venom helped decrease the population of ovarian cancer cells. The mechanism recorded was: caspase activation through the mitochondrial pathway, inhibition of Bcl2 and ROS accumulation. An increase in the expression of caspase (3 and 9) and a downregulation of Bcl2 indicated that this treatment possesses anti-tumor activity established by the intrinsic apoptotic pathway.
All of the studies, discussed above, indicate that the toxins obtained from bee venom can serve as a potential candidate for treating subjects of ovarian cancer. The bee venom bioactive compounds were studied carefully to explore their anti-cancer therapeutic properties. Still, it is essential to search in detail anti-cancer traits of bee venom through different clinical studies, which could help the researchers have a better understanding of the molecular action of these toxins on cancer cells.
The Synergistic Cytotoxic Effect of Cisplatin and Honey Bee Venom on Human Ovarian Cancer Cell Line A2780cp
There is a huge population of women suffering from different types of cancer and ovarian cancer is one of them. Bee venom is a well-known naturally occurring therapeutic agent for its medicinal benefits. While cisplatin can be described, as one of the best chemotherapeutical compounds that help in treating ovarian cancer. This study was devised to examine the synergistic and cytotoxic effects of BV along with cisplatin on the A2780cp cells (ovarian cancer cisplatin-resistant cells).
To conduct this experiment an immunocytochemical and flowcytometric analysis, DNA fragmentation assay, morphological examination, and MTT assay were conducted. The MTT assay showed that a dose of 8µg/mL of bee venom and 25mg/mL of cisplatin and 4µg/mL of bee venom and 10mg/mL of cisplatin maintained for 24 hours lead to the death of A2780cp cells by nearly 50%.
While the biochemical or morphological examination showed that the apoptotic manner of cell death was induced by cisplatin and bee venom when used in combination and also separately. Immunocytochemical and flowcytometric analysis indicated a visible reduction in the level of Bcl2 protein. Of all the clinical findings recorded, it was declared that different components of bee venom exert an anti-cancer effect on the human ovarian cancer cells. That eventually established that bee venom also carries the potential for enhancing and generating a cytotoxic effect of cisplatin – anti-tumor agent.
Conclusion:
The results compiled are by other clinical studies conducted on the U937 cells and MCF7 cells, which also showed that BV leads to apoptotic death of cells in the prostate carcinoma LNCaP, PC3, and DU145 cells through activating caspase3 by inactivating of in vivo and in vitro.
Researchers also put forward that this anti-cancer trait of bee venom was linked with a hike in the levels of anti-apoptotic and proliferative gene products that include cPLA2, COX-2, iNOS, XIAP, clap-2, and Bcl-2, which are all regulated by the NFκB.
According to the results gathered, BV can easily be used to enhance the cytotoxic effect of customary chemotherapeutic agents.
What are the reasons that cause ovarian cancer?
Ovarian cancer is caused due to different risk factors that are associated with: multiple ovulation periods, few pregnancies, infertility, late menopause, and early menopause. In the same manner, different natural factors protect from ovarian cancer like having several pregnancies, making proper use of contraceptives, breastfeeding and undergoing sterilization or ovarian removal. Lifestyle factors like having a normal BMI index and an active lifestyle also helps in getting rid of the risk of catching ovarian cancer. There are also hereditary variants that lead to ovarian cancer.
Elaborating further, BRCA1 and BRCA2 mutation most commonly develops a risk for women to become a victim of ovarian cancer or breast cancer. On the other hand, inherited mutations, which have any sort of link to other forms of cancer, in both women and men, can also indicate an increased risk of catching ovarian cancer. It is to be noted that most of the women, who are more than 50 years of age are diagnosed with this type of cancer.
Anticancer Activity of Toxins from Bee and Snake Venom—An Overview on Ovarian Cancer
Cancer is one of the most problematic diseases when it comes to a public health concern. Angiogenesis is an abnormal proliferation of tumor responsible cells and there is a complex relationship between different cancer cells and components of the extracellular matrix, which can be regarded as an important development of the phase of carcinogenesis. This pathway of this action is being examined to develop an effective anti-cancer treatment.
According to different clinical studies, it has been found that toxins contained in different types of venoms generate an anti-cancer effect on the human cancer cell threads. This provides a new prospect in the field of developing anti-cancer drugs.
In this study, the effect of natural toxins contained in snake and bee venom was scrutinized under a special therapy regime to understand their mechanism that prevents the proliferation and growth of cancer cells. During this research, various molecules were studied from the venom source that can contain ovarian cells that lead to ovarian cancer. It was found that especially bee venom contains several helpful toxins that can pave a way for developing a safe anti-cancer therapy that could be followed instead of conventional chemotherapy that has several dangerous side effects.
This study can help improve the effectiveness of the standard anti-cancer therapies and also regulate a proper dose of chemotherapy that could be less dangerous for the patients of ovarian cancer. Such types of studies, which rely on using natural sources, for treating the gravest diseases and illnesses are immediately required to bring some relief for the patients suffering from different types of cancers. These studies, carried out in-depth, also help explore the molecular mechanism of toxins on the cancer cells.
Bee venom activity
Bee venom contains different active compounds that possess pharmaceutical activities. Most useful are the carbohydrates (non-peptic compounds) and peptides that include adolapin and apamin, MCD (mast cell de-granulating peptide, melittin, phospholipase A2 (enzymes) and biogenic amines (norepinephrine, dopamine, and histamine). Most of the clinical studies are conducted to explore the effect of these bee venom compounds that carry the biological activity.
Through Melittin
Melittin is regarded as the main element of bee venom. It is a complex protein that has 26 amino acid residues. It can be easily dissolved in water and it also has been found that it disrupts and integrates the phospholipid bilayers (synthetic and natural). In the view of different reports, it can be deduced that melittin certainly delivers different effects like anti-viral, anti-inflammatory, anti-bacterial properties and prevent the progression of malignant cells, apoptosis, and cell cycle arrest.
Through Apamin
Apamin is the second most important element of bee venom and it has 10 amino acids that have two disulfide bonds. It is also known as the smallest existing neurotoxin in BV. Apamin’s main effect is; categorized inhibition of the Ca2+ activated K+ channels. What an apamin does is that it blocks all the channels through minimum concentration and enhances neuronal excitability and plasticity.
According to a scholarly research article, Ichii et al, it was reported that apamin effects tracheal contraction by releasing histamine from the lung tissues and that ultimately helps in decreasing allergic inflammation of the airway. A study conducted in 2003, showed that apamin also prevents nitric oxide generated relaxation of myometrium in expecting mothers.
Through MCD
MCD is another important compound that contains 22 amino acids and carries 2 disulfide bonds between the Cys5, 19 and Cys3, 15. MCD prevents the production of histamine from the mast cells under minimum concentrations carrying the anti-allergic activity. Studies reveal that this process of inhibition of histamine is fairly possible when the concentration administered is in a larger volume than the naturally released quantity of histamine. The reason is that it comes in action with the immunoglobulin E-molecule.
Through Adolapin
There is another useful peptide, called adolapin that carries analgesic, antipyretic and anti-inflammatory properties and also prevents the activity of bee venom phospholipase A2. Adolapin carries this trait because; it inhibits the prostaglandin synthesis process by cyclooxygenase inhibitory characteristics.
Effect of Bee Venom on Cancer Cells
Through its different mechanisms, bee venom induces apoptosis of the malignant cells and prevents the growth of the tumor. Phospholipase A2 activation with the help of melittin is generally regarded as the most crucial mechanism of bee venom. According to Gajski, it was recorded that melittin certainly has inhibitory effects on calmodulin as an anti-proliferation agent of BV. It also leads to an enhanced PLA2 activity, necrosis and calcium influx.
A study concluded that general activity of bee venom on different types of cancer-causing cells is carried out by compounds that induce apoptosis through activation of caspase-3 and caspase-9 or by releasing AIF and EndoG from mitochondria. Researchers, belonging to this study, also investigated in detail the molecular mechanism of bee venom that induces apoptosis in the human bladder cancer cells. It was found that there are different pathways like promoting activation of initiating effector-caspase and caspases with the Fas/CD95 (adaptor proteins), inducing the release of the reactive oxygen species and the ER and Ca2+ stress-mediated apoptotic death and behaving as a receptor for the bee venom.
A study was conducted in 2010, regarding lung cancer that determined that various compounds of BV carry anti-angiogenic effects, as they block the tyrosine phosphorylation of VEGFR2. In this study, the molecular mechanism of melittin, in link with its pharmacological activity, was also observed in the leukemic U937 cells. It was concluded that bee venom generates down-regulation of Akt and ERK signal pathways by caspase-3 and Bcl-2 acting as the main regulators that induce apoptosis.
A study carried out in 2012, examined thoroughly the cytotoxic effect of BV in combination with the cisplatin on cisplatin-resistant cancer cells (A2780cp cells). Treatment was carried out by administering 8µ/mL of BV or 25mg/mL of cisplatin for nearly 24 hours that resulted in the death of cisplatin-resistant cancer cells by 50%.
A simultaneous treatment also delivered the same results, where cisplatin was maintained at 10mg/mL and bee venom was administered at 4µg/mL for nearly 24 hours. The researchers investigated the effect on the expression of Bcl2 that showed a decrease in the cisplatin-resistant cancer cells after the cells were subjected to cisplatin and bee venom.
This study concluded that bee venom has a positive effect on ovarian cancer cells and also enhanced the cytotoxic effect on cisplatin, which is an anti-tumor agent.
According to another study carried out in 2015, the pro-apoptotic and cytotoxic effect of chrysin and bee venom was examined on the cisplatin-resistant ovarian cancer cells. For the clinical study, chrysin was given at 40µg/mL and bee venom at 8µg/mL while, a combination of chrysin and bee venom at 15µg/mL and 6µg/mL respectively, resulted in the death of cisplatin-resistant ovarian cancer cells by 50%.
The study done above is by Alizedehnohi et al. carried out about the downregulation of Bcl-2. Researchers of this study established that there is a special mechanism through which chrysin and bee venom helped decrease the population of ovarian cancer cells. The mechanism recorded was: caspase activation through the mitochondrial pathway, inhibition of Bcl2 and ROS accumulation. An increase in the expression of caspase (3 and 9) and a downregulation of Bcl2 indicated that this treatment possesses anti-tumor activity established by the intrinsic apoptotic pathway.
All of the studies, discussed above, indicate that the toxins obtained from bee venom can serve as a potential candidate for treating subjects of ovarian cancer. The bee venom bioactive compounds were studied carefully to explore their anti-cancer therapeutic properties. Still, it is essential to search in detail anti-cancer traits of bee venom through different clinical studies, which could help the researchers have a better understanding of the molecular action of these toxins on cancer cells.
The Synergistic Cytotoxic Effect of Cisplatin and Honey Bee Venom on Human Ovarian Cancer Cell Line A2780cp
There is a huge population of women suffering from different types of cancer and ovarian cancer is one of them. Bee venom is a well-known naturally occurring therapeutic agent for its medicinal benefits. While cisplatin can be described, as one of the best chemotherapeutical compounds that help in treating ovarian cancer. This study was devised to examine the synergistic and cytotoxic effects of BV along with cisplatin on the A2780cp cells (ovarian cancer cisplatin-resistant cells).
To conduct this experiment an immunocytochemical and flowcytometric analysis, DNA fragmentation assay, morphological examination, and MTT assay were conducted. The MTT assay showed that a dose of 8µg/mL of bee venom and 25mg/mL of cisplatin and 4µg/mL of bee venom and 10mg/mL of cisplatin maintained for 24 hours lead to the death of A2780cp cells by nearly 50%.
While the biochemical or morphological examination showed that the apoptotic manner of cell death was induced by cisplatin and bee venom when used in combination and also separately. Immunocytochemical and flowcytometric analysis indicated a visible reduction in the level of Bcl2 protein. Of all the clinical findings recorded, it was declared that different components of bee venom exert an anti-cancer effect on the human ovarian cancer cells. That eventually established that bee venom also carries the potential for enhancing and generating a cytotoxic effect of cisplatin – anti-tumor agent.
Conclusion:
The results compiled are by other clinical studies conducted on the U937 cells and MCF7 cells, which also showed that BV leads to apoptotic death of cells in the prostate carcinoma LNCaP, PC3, and DU145 cells through activating caspase3 by inactivating of in vivo and in vitro.
Researchers also put forward that this anti-cancer trait of bee venom was linked with a hike in the levels of anti-apoptotic and proliferative gene products that include cPLA2, COX-2, iNOS, XIAP, clap-2, and Bcl-2, which are all regulated by the NFκB.
According to the results gathered, BV can easily be used to enhance the cytotoxic effect of customary chemotherapeutic agents.
Sources:
Anticancer Activity of Toxins from Bee and Snake Venom—An Overview on Ovarian Cancer
The synergistic cytotoxic effect of cisplatin and honey bee venom on human ovarian cancer cell line A2780cp
Metabolomic Profiling of the Synergistic Effects of Melittin in Combination with Cisplatin on Ovarian Cancer Cells
Metabolomic Profiling of the Effects of Melittin on Cisplatin Resistant and Cisplatin Sensitive Ovarian Cancer Cells Using Mass Spectrometry...
Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells.
Anticancer Activity of Toxins from Bee and Snake Venom—An Overview on Ovarian Cancer
The synergistic cytotoxic effect of cisplatin and honey bee venom on human ovarian cancer cell line A2780cp
Metabolomic Profiling of the Synergistic Effects of Melittin in Combination with Cisplatin on Ovarian Cancer Cells
Metabolomic Profiling of the Effects of Melittin on Cisplatin Resistant and Cisplatin Sensitive Ovarian Cancer Cells Using Mass Spectrometry...
Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells.
