As one of the most common causes of death among cancers of females, the ovarian cancer has a case fatality rate ranking first in gynecologic malignant tumors. The deaths in the 238,700 ovarian cancer cases newly found in the world every year are as high as 151,900. Ovarian cancer has insidious early symptoms, and often shows distant metastasis before occurrence of symptoms; 60%~70% patients have been at the advanced stage when seeing their doctor. The first-line chemotherapy regimens for ovarian cancer are the therapeutic regimens based on platinum and taxanes, however, more than 2/3 patients still have the risk of recurrence after using such therapeutic regimens and eventually die because of chemotherapy resistance. Therefore, it is of great clinical significance and social value to find new ovarian cancer drugs.

Natural products have aroused great interest of the broad science researchers owing to the high antitumor activity and low toxicity. The TCM Atractylodes macrocephala is the dry rhizome of the perennial herb Atractylodes macrocephala that belongs to atractylodes of asteraceae, is a common TCM, with efficacy like tonifying Qi and strengthening the spleen, and removing dampness and inducing diuresis, and is clinically usually used for spleen deficiency syndrome. According to modern pharmacology research, it mainly contains volatile oil and lactones, wherein, the latter plays the anti-inflammatory and anti-tumor role and has the efficacy of regulating gastrointestinal function and promoting nutrient absorption.

The Atractylenolide I (AT-I) is a sesquiterpene lactone compound and one of the main active ingredients of Atractylodes macrocephala. It possesses extensive pharmacological and biological activities, such as anti-inflammatory, anti-oxidative stress and antitumor effects, however, there are not many studies on the antitumor effect of AT-I on ovarian cancer, and its antitumor molecular mechanism is unclear. A recent article published on the Medical Science illustrates the mechanism of action of AT-I in inhibiting proliferation of ovarian cancer cells, and provides basis for the clinical application of AT-I, and also new thought for the R&D of other ovarian cancer drugs.

Fig. 1 Structure formula of AT-I

The research used AT-I to act on SK-OV-3 and OVCAR-3 cells in human ovarian cancer, and revealed the mechanism of action of AT-I by detecting the cell viability, cell cycle-related protein and cell cycle-related signaling pathway change condition: separately 24h, 48h and 72h after having AT-I of difference concentrations (0, 5, 10, 20, 40, 80, 160 μ M) act on SK-OV-3 and OVCAR-3 cells in human ovarian cancer, the cell viability was detected through MTT (Fig. 2), and the results showed that 20 μ M AT-I was enough to significantly inhibit the SK-OV-3 cell viability, and as the concentration and acting time of AT-I increased, the inhibiting effect became stronger. Likewise, after 72h of action of 20 μ M AT-I, the OVCAR-3 cell viability was significantly inhibited, and as the concentration and acting time of AT-I increased, the inhibiting effect became significantly stronger. Those results showed that the inhibition of AT-I on SK-OV-3 and OVCAR-3 cell proliferation was concentration and time dependent.

Fig. 2 Inhibition of AT-I on proliferation of SK-OV-3 and OVCAR-3 cells of ovarian cancer

a: Inhibition of AT-I on proliferation of SK-OV-3 cells; b: Inhibition of AT-I on proliferation of OVCAR-3 cells

In treating the SK-OV-3 and OVCAR-3 cells of ovarian cancer with AT-I of difference concentrations (0, 10, 20, 40μM), the analysis results of the flow cytometry showed that 20 and 40 μ M AT-I could significantly reduce the proportion of cells in S phase of SK-OV-3 cells, and increase the proportion of cells in G2/M phase; in addition, 40 μ M AT-I could significantly reduce the proportion of cells in S phase of OVCAR-3 cells, and increase the proportion of cells in G2/M phase (Fig. 3).

Fig. 3 Influences of AT-I on cycles of SK-OV-3 and OVCAR-3 cells of ovarian cancer

a: Influences of AT-I on cycle of SK-OV-3 cells of ovarian cancer; b: Influences of AT-I on cycle of OVCAR-3 cells of ovarian cancer

We can find in the above research that AT-I could inhibit the proliferation of SK-OV-3 and OVCAR-3 cells of ovarian cancer, and the inhibition of AT-I on proliferation of those two kinds of cell was concentration and time dependent: as the concentration and acting time of AT-I increased, the proliferation inhibiting effect became more obvious.

The most fundamental biological characteristic of malignant tumors is the uncontrolled proliferation of tumor cells, and the biological foundation of uncontrolled cell proliferation is the cell cycle regulation disorder, therefore, blocking progress of tumor cell cycle and inhibiting tumor cell proliferation are of great significance to the tumor treatment. Chinese and foreign scholars have made in-depth studies on Atractylodes macrocephala in recent years, and made great achievements, in particular, the studies on the lactones of Atractylodes macrocephala: some have gone deep into the cell gene level. However, studies have not involved much of the clinical efficacy of Atractylodes macrocephala, and there is no quantitative index in its quality standard research. Those require scholars to conduct deeper research on Atractylodes macrocephala, especially they shall pay attention to its water decoction efficacy and material basis.

Reference: Long F. et al. Anti-tumor effects of Atractylenolide-I on human ovarian cancer cells. Med Sci Monit, 2017; 23: 571-579.

By Ye Fenghong