A new study reveals ginger contains a pungent compound that could be up to 10,000 times more effective than conventional chemotherapy in targeting the cancer stem cells at the root of cancer malignancy.
A new study published in PLoS reveals a pungent component within ginger known as 6-shogaol is superior to conventional chemotherapy in targeting the root cause of breast cancer malignancy: namely, the breast cancer stem cells.
Study named : 6-Shogaol Inhibits Breast Cancer Cells and Stem Cell-Like Spheroids by Modulation of Notch Signaling Pathway and Induction of Autophagic Cell Death
The new study titled, “6-Shogaol Inhibits Breast Cancer Cells and Stem Cell-Like Spheroids by Modulation of Notch Signaling Pathway and Induction of Autophagic Cell Death,” identified powerful anti-cancer stem cell activity in 6-shogaol, a pungent constituent of ginger produced when the root is either dried or cooked. The study also found that the cancer-destroying effects occurred at concentrations that were non-toxic to non-cancerous cells – a crucial difference from conventional cancer treatments that do not exhibit this kind of selective cytotoxicity and therefore can do great harm to the patient.
The authors of the study further affirm these points: Cancer stem cells pose serious obstacle to cancer therapy as they can be responsible for poor prognosis and tumour relapse. To add into the misery, very few chemotherapeutic compounds show promise to kill these cells. Several researchers have shown that cancer stem cells are resistant to paclitaxel, doxorubicin, 5-fluorouracil, and platinum drugs [8, 16]. CSCs are thus an almost unreachable population in tumours for chemotherapy. Therefore any compound, that shows promise towards cancer stem cells, is a highly desirable step towards cancer treatment and should be followed up for further development.
The researchers identified a variety of ways by which 6-shagoal targets breast cancer: It reduces the expression of CD44/CD24 cancer stem cell surface markers in breast cancer spheroids (3-dimensional cultures of cells modeling stem cell like cancer)
It significantly affects the cell cycle, resulting in increased cancer cell death
It induces programmed cell death primarily through the induction of autophagy, with apoptosis a secondary inducer
It inhibits breast cancer spheroid formation by altering Notch signaling pathway through γ-secretase inhibition.It exhibits cytotoxicity (cell killing properties) against monolayer (1-dimensional cancer model) and spheroid cells (3-dimensional cancer model)
It was in evaluating the last mode of 6-shagoal’s chemotherapeutic activity and comparing it to the activity of the conventional chemotherapeutic agent taxol that the researchers discovered an astounding difference. Whereas taxol exhibited clear cytotoxicity in the one-dimensional (flat) monolayer experimental model, it had virtually no effect on the spheroid model, which is a more “real world” model reflecting the 3-dimensionality of tumors and their stem cell subpopulations. Amazingly, this held true even when the concentration of taxol was increased by four orders of magnitude:
Ginger (Zingiber officinale) is a well known herb consumed as a spice and food as well as widely used as herbal medicine for various ailments. A number of biologically active ingredients including gingerols and its various derivatives have been identified and synthesized from ginger in recent years. One important class of derivatives are shogaols that are primarily the dehydrated products of gingerols and are found exclusively in dried ginger. Among the shogaols, 6-shogaol has achieved a great deal of attention due to its potent anticancer activity against various cancer cells. It has been shown to induce mitotic arrest and reduce viability of gastric cancer cells . Aberrant mitosis followed by apoptosis has also been found to be induced by 6-shogaol in HCT-116 colon cancer cells. In human hepatoma p53 mutant Mahlavu subline, 6-shogaol induces apoptosis via oxidative stress pathway in a caspase dependent mechanism. It has also been shown to induce autophagy in HNSCLC A-549 cells via inhibition of the AKT/mTOR pathway . In another study, 6-shogaol has been reported to exhibit anti-invasive effects in breast cancer cells by reducing MMP-9 expression through NF-κB activation. Recently, PPAR-γ dependent apoptosis in MCF-7 and HT-29 cells by 6-shogaol has also been reported. Additionally, recent studies have implicated microtubule as a possible target of 6-shogaol as it interacts with the sulphydryl groups of cysteines in tubulin through its side chain containing the α, β unsaturated carbonyl moiety . All these studies place 6-shogaol as a promising agent to be studied further in view of its future therapeutic potential in cancer therapy.
Cancer stem cells play a very important role in cancer development and progression. The concept of stem cell origin of cancer has been supported by observations that certain subpopulations (only 0.2–1%) of cancer cells have stem cell-like properties, such as the ability to self renew, continuous differentiation and an overall innate resistance to conventional chemotherapeutic agents. These chemo-resistant, self-renewing, tumorigenic sub-population of cells defined as cancer stem cells (CSCs) play crucial roles in cancer recurrence. CSCs have been identified in various solid tumors including breast, ovarian, head and neck, pancreas, and colon cancer Earlier studies demonstrated that the signaling pathways such as Wnt/β-catenin, Notch and Hedgehog pathways regulate the growth of cancer stem cells . Therefore, targeting these pathways is considered to be a useful strategy to inhibit cancer stem cell regeneration.
Although, CSCs are present in a very small percentage in the total tumour, methods have been developed to grow them in large population in ex vivo. In appropriate growth conditions, cancer cells can be made to grow in the form of spheroids. These spheroid-forming cells exhibit altered cell surface markers when compared to cells grown in monolayer culture and have been shown to possess stem-cell like properties [10, 13]. These spheroids have been used in a number of studies to determine the in vitro and in vivo characteristics of cancer stem cells as well as to assess the inhibitory activity of cytotoxic compounds against cancer stem cells
Several in vitro studies have shown that cancer stem cells are resistant to conventional chemotherapeutic drugs . Interestingly, a number of dietary compounds like curcumin, piperine , sulforaphane have recently been identified to target CSCs. However, various factors such as toxicity, weak dose response etc. largely limit their application. Since 6-shogaol has been reported as a potent anticancer agent against various cancer cells, we have investigated its inhibitory effect on breast cancer cells and cancer stem cell-like spheroids. Here we demonstrate that 6-shogaol shows anti-proliferative activity against breast cancer cells and spheroids and suppresses the size and colony forming ability of spheroids by altering the Notch signaling pathway. Investigation of the death mechanism shows that autophagy is a predominant mode of cell death caused by 6-shogaol in breast cancer cells.