14 1.3 Vitexin: A Promising Anti-Tumour Treatment?

Symptomology: Good or Bad?

Cytotoxicity

There has been debates about whether or not toxicity is a key factor in clinical outcomes of cancer treatments and if it predicts favorable outcomes.^[2] Toxicity can involve clinical outcomes such as a rash, gastrointestinal toxicity, and myelosuppresion.^[3] Toxicity have been found to have good implications. For example, patients exhibiting neutropenia and non-small lung cancer have increased survival rates with certain toxic therapies.^[4] However, toxicity has also have been with negative implications. Treatment can lead to myelosuppression, which disadvantages the clinical outcomes of patients.^[5][6] Another example of cytotoxicity-associated outcomes can be seen in the case of peripheral neuropathy. The presence of peripheral neuropathy can lead to improved results for those with ovarian cancer, but not for patients with breast cancer. In a study done by Abola, Prasad, & Jena (2014), results indicated that greater toxicity treatments induced greater clinical efficacy. The effect was dependent on the type of toxicity. Although achieving high efficacy is favourable, the unfortunate aspect of high cytotoxic treatments are the greater injury that may cause more suffering to patients.^[7] Therefore, finding a low toxicity treatment with high efficacy is important, so that patients can undergo less symptomatic-effects, whilst achieving tumour-growth inhibition.

Vitexin: A Low Cytotoxic Treatment

Vitexin is known to present low cytotoxic effects, with beneficial pharmacological effects such as anti-oxidant, anti-cancer, anti-inflammatory, and neuroprotective outcomes.^[8] After repeated treatment of vitexin during a 7-day period on liver and gastric injuries, no adverse symptoms were present.^[9] In another study looking at the inhibition of neutrophil migration induced by vitexin, researchers found that vitexin caused the inhibition of pro-inflammatory mediators, resulting in no damaging consequences.^[10] This signifies that vitexin is a safe treatment, with similar anti-proliferation effects as high cytotoxic treatments.

Though vitexin has low cytotoxicity, research is still required for understanding it’s full pharmacokinetic effects.^[11] So far, what is understood is that intravenous and oral administration of vitexin causes wide and rapid distribution of the drug across different tissues.^[12] Oral administration of vitexin causes poor absorption by the gastrointestinal tract, allowing it to directly reach the colon.^[13][14] Vitexin treatment given intravenously, resulted in most of the drug appearing in the liver and kidney. It was least likely to be seen in fatty areas and in the brain of rats.^[15] For cancer treatment, oral administration may not be an effective method if it has a low bioavailability. However, when injected, there is a more body-wide distribution of vitexin. In conjunction with the in vivo results of Liu et al’s (2019) study, testing various methods of administering vitexin may help determine the most effective treatment procedure.

Vitexin and Other Cancer Cells

This study is consistent with most studies, as vitexin has been seen to induce apoptosis in other carcinoma cells:

^[20]

Current Cancer Treatments

There are many potential treatments being researched to determine which pathways can be targeted to prevent cancer cell proliferation:

mTOR

mTOR  is seen as an attractive target for many anti-cancer treatment. In previous studies, mTOR has been targeted by using anti-fungal agents such as rapamycin (branded Sirolimus). Rapamycin was originally used to treat cancers, but was later deemed unfavourable due to its negative effects on the human body. However, rapamycin has been developed into different agents, including temsirolimus, everlimus, and ridaforolimus. Each agent functions intracellularly by attaching to the FK506 binding protein. This forms a complex, which is recognized by mTOR, leading to the inhibition of cellular survival and cell cycle progression. The differences of these agents lead to various pharmacokinetic profiles that are dependent on the location of the cancer cells. For example, neuroendocrine tumors, breast cancers, and so forth, each have different optimal drugs needed for treatment.^[21]

Bcl-2

Venetoclax is a chemotherapeutic drug that is currently used as a Bcl-2 inhibitor. This drug has been used as a treatment method for other cancers, such as chronic lymphocytic leukemia and small lymphocytic lymphoma. Although side effects include nausea, the reduction of white blood cells, diarrhea, and tumour lysis syndrome. Tumour lysis syndrome can lead to kidney failure as a result of the release of uric acid, potassium, and phosphorous due to rapid death of several cancer cells.^[22][23]

Other Flavonoids and Their Effects

Alongside vitexin, other natural compounds have also explored for their known benefits (Liu et al, 2019). High fruit and vegetable diets are associated with lower risk of common cancers such as breast, prostate, and colon cancers.^[24] The bioactive compounds leading to chemoprotective effects within these plants are unknown. Flavonoids are being researched as potential cancer prevention compounds.^[25]

The following are some examples of flavonoids under investigation as potential anti-tumour treatments:

Tubeimoside-1: similar to vitexin, TBMS1 has also been used as a traditional Chinese herbal medicine.

Jia et al (2015) looked at the efficacy of TBSMI as a potential cancer treatment against glioma tumour cells. Glioma are a form of inter-cranial tumours, accounting for close to majority of brain-spinal cancers, they also have a very low cure rate and high mortality rate. In this study, the effects of TBMS1 inhibited the glioma tumour proliferation in a time and dose-dependant manner, much like Liu et al’s (2019) study in regards to vitexin. Similarly effecting the same pathways: upregulating bax, while reducing expression in bcl-2, leading to the release of cytochrome c and cleavage of caspase-3 resulting in apoptosis. ^[26]

Orientin: a flavonoid monomer in the plant Trollius chinensis bunge, alongside vitexin. Orientin contains a similar chemical makeup to vitexin and has anti-thrombus and antioxidant properties. This flavonoid has been tested as a potential anti-tumor therapy treatment against esophageal cancer cells in a study done by Fang et al (2015), indicated that orientin had exhibited stronger anti-tumour effects compared to vitexin using the same concentration.^[27]

EGCG: epigallocatechin-3-gallate is a flavonoid found in green tea, and has been heavily researched for its ability to induce apoptosis and inhibit cancer cell proliferation for carcinomas such as HeLa cervical cells, laryngeal squamous carcinoma cells, melanoma cells, and A549 cells. However, the downstream mechanisms inducing apoptosis varies between cell lines; therefore, apoptosis can be completed through mitochondrial-dependent pathways, endoplasmic-dependent pathways, or extrinsic pathways (through cell-death receptor).^[28]