With the medical field growing and discovering new technologies to help patients, the concerns for the adverse side effects and negative impacts of various therapies still remain in the minds of doctors and scientists. There is an urgent need of alternative therapies and medications which are far less lethal and in some cases can cure better than the current treatments.
Many people believe that it is an untreatable disease with no cure. But, it is seen that this view is overly exaggerated. By no means this article states that cancer is less lethal. According to the ACS (in 2010), There will be 1.5 million new cases of cancer occurring in the United States coming year, and over 570,000 deaths because of it not including basal and squamous skin cancers which are not reported but could add another two million. While the diagnosis for cancer may still stress out some of the patients, in many cases there is cause for hope.
In this article, we will talk about the alternative treatment for cancer, specifically Ocimum sanctum (OS), its mechanism of action, its effects, and finally we will talk to Pulkit Kumar and Dhaniket Patel, who are researchers at the University of Alberta, Canada and are involved in the development of alternative therapies to sustain the future.
What is Ocimum sanctum (OS)?
OS is a medicinal herb found in the semi tropical and tropical parts of India. It has been widely used in Ayurvedic system of medicine for its various medicinal properties including but not limited to infections, skin and liver disorders and as an antidote for snake and scorpion bites. It has been used as an anti-inflammatory, immunomodulatory, anti-infective, anti-stress, antipyretic, antitussive, anti-diabetic, cardioprotective, neuroprotective and hepatoprotective agent. Although every part of this plant has been studied and has been suggested to have therapeutic uses, the leaves in particular have been extensively studied. The leaves of OS are a source to an essential oil and when mixed with ethanolic extract, it was found to have antioxidant properties.
Few studies have also demonstrated the potential of OS as an anti-tumor agent. In a comparison study of cytotoxic activity, the essential oil was compared with 17 Thai medicinal plants, results showed that OS was most effective in inhibiting the proliferation of human oral squamous cell carcinoma (KB) and mouse leukemia cells (P388) in vitro. Further studies have confirmed that the extract exhibited a cytotoxic effect against A549 lung cancer cells, cleaved the pro-apoptotic molecule poly-(ADP-ribose) polymerase (PARP), promoted the release of cytochrome C, increased the activity of caspases 3 and 9 and the ratio of Bax/Bcl-2. Furthermore, it also decreased the rate of proliferation by decreasing the cells in G2/M phase. The extracts also inhibited the invasion of murine Lewis lung cancer (LLC) cells in vitro associated with a decrease in the activity of matrix metalloproteinase-9 (MMP9). On the other hand, in vivo metastatic lung nodules following injection of LLC cells in the tail vein. In summation, the above mentioned studies conclude that extract from leaves of OS can induce apoptosis, inhibit cell cycle progression and prevent metastasis.
Active phytochemicals in OS include cirsilineol, cirsimaritin, isothymusin, apigenin and rosmeric acid and appreciable quantities of eugenol. The leaves also contain orientin, vicenin, ursolic acid, apigenin, luteolin, apigenin-7-O-glucuronide, luteolin-7-O glucuronide and molludisti. It is also known to possess αelemene, neral, myrtenal, α- and β-pinenes, camphene, campesterol, stigmasterol and β-sitosterol. Most of these phytochemicals are known for their diverse benefits in pharmacological studies. When it comes to the mechanism of action, the precise mechanism of OS is not known but generally it is believed that OS is generally helpful in mediating different types of cancers by increasing the antioxidant activity, altering the gene expressions, inducing apoptosis, and inhibiting angiogenesis and metastasis. Phytochemicals like eugenol are also known to prevent radiation-induced DNA damage. The rest of the review will focus on the different types of cancers and how OS mitigated them at cellular level.
General Mechanism of Action
Adding on to the vast benefits of the ethanolic extracts of OS, it is also shown that the extract has cytotoxic and apoptosis-inducing effects in human fibrosarcoma cells in vitro. In human fibrosarcoma cells, the cytotoxicity was not significant at lower concentrations (<50 μg/ml). However with increase in concentration, the cytotoxic effects increased exponentially. OS caused oxidative stress as a decrease in the levels of free GSH with concomitant increase in the levels of products of lipid peroxidation was seen. Both the aqueous and the ethanolic extracts were shown to reduce the tumor volume and increase the lifespan of the Sarcoma-180 bearing animals, which means that the observed in vitro observations extended to the animal system as well.
OS as a Radioprotective Agent
The extract of OS is shown to prevent radiation induced chromosomal damage and to enhance the bone marrow stem cell survival more effectively than WR-2721 (300 mg/kg). Additionally, when compared with the cohorts that received either OS or WR 271, the group administered with both OS and WR-2721 before exposure to radiation had decreased the number of chromosomal damage and more number of bone marrow stem cells. Mechanistic studies have shown that OS mediates its protective effects by scavenging free radicals to reduce the levels of radiation-induced lipid peroxidation and to concomitantly increase the levels of the antioxidant molecule GSH and the antioxidant (GSRx, GSPx, and SOD) and phase 2 enzymes (GST). The aqueous extract of OS (40 mg/kg body weight for 15 days) is also shown to protect mice against the oxidative stress induced by high-doses (3.7 MBq) of 131I. Administering OS reduced the levels of lipid peroxidation and prevented depletion of GSH in both kidneys and salivary glands. Oral administration of the hydroalcoholic extract (200 mg/kg body weight) has also been reported to reduced GSH levels and activity of GST in C57BL mice.
Current Researches on OS
Pulkit Kumar and Dhaniket Patel are researchers at the University of Alberta, who have concerns about the current treatments and are involved in developing and discovering new methods to treat patients with little to no side effects. The duo said that it is really important to keep innovating in a way that brings maximum positive results to the people with much less production cost of the medicine when compared to the current therapies. They have specifically emphasized on the human control trial of these medicines to test how effecitve they are, to understand their mechanism of action and to really check for any reactions in the body after consuming these. Their main concerns also include that even though there have been so many proposed alternative treatments, very few human control trials are actully conducted and there isn't much funding given to the researchers, when it comes to the field of alternative therapies.
They have also said that human control trials are important to fill gaps about the research so that people are well informed about the medications or treatments they are receiving. They have decided to conduct an animal control trial of the medication proposed followed by a human control trial.