Synergistic Genotoxic Effects and Modulation of Cell Cycle by Ginger Ethanolic Extracts in Adjunct to Doxorubicin in Human Lymphocytes In Vitro
Treetip Ratanavalachai PhD*, Sumon Thitiorul MS**, Sermkiat Tanuchit MS***, Wantha Jenkhetkan MS****, Arunporn Itharat PhD*****, Intouch Sakpakdeejaroen MS*****
Affiliation : * Division of Biochemistry, Department of Preclinical Science, Thammasat University, Pathumthani, Thailand ** Division of Anatomy, Department of Preclinical Science, Thammasat University, Pathumthani, Thailand *** Reseach Center, Thammasat University, Pathumthani, Thailand **** PhD Graduate Program, Division of Biochemistry and Molecular Biology, Thammasat University, Pathumthani, Thailand ***** Division of Applied Thai Traditional Medicine, Faculty of Medicine, Thammasat University, Pathumthani, Thailand
Background : Several natural phytochemicals are increasingly used, as an adjunct to chemotherapy, to reduce drug adverse
effects. Zingiber officinale rhizome (ginger) product has been reported to be effective against nausea and vomiting in patients
receiving emetogenic chemotherapy such as cisplatin/doxorubicin (DXR). In addition, its ethanolic extract of Zingiber
officinale rhizome (EEZOR) has been reported to possess anticarcinogenic properties. However, the mechanism for anticancer
activity of ginger especially when used in combination with chemotherapy has not well elucidated, one of its possible
mechanisms might involve its genotoxicity.
Objective : To investigate genotoxic and cytotoxic potentials of EEZOR alone and EEZOR pretreatments followed by 0.1 mcg/
ml DXR, a genotoxic chemotherapeutic agent in human lymphocytes by sister chromatid exchange (SCE) assay in vitro. The
effect on cell cycle kinetics was also explored.
Material and Method: Human lymphocytes were treated with EEZOR alone at 25-500 mcg/ml and EEZOR pretreated at
12.5-200 mcg/ml followed by 0.1 mcg/ml DXR. SCE levels and cell cycle kinetics were evaluated.
Results : EEZOR significantly induced biphasic SCE at 50 and 400 mcg/ml (p<0.05). However, cytotoxicity manifested at 500
mcg/ml. All EEZOR pretreatments at 12.5, 25, 50, and 100 mcg/ml, except at 200 mcg/ml, prior to DXR, moderately enhanced
DXR-induced genotoxicity by 1.3 times (p<0.05). Both EEZOR alone and EEZOR prior to DXR at certain concentrations
delayed cell cycle.
Conclusion : At specific doses, EEZOR could induce genotoxicity and in pretreatments could moderately enhance DXR-
induced genotoxicity and delay cell cycle. This finding suggests that dosage use of EEZOR needs to be adjusted for long-term
safety. In addition, EEZOR in adjunct to DXR might have potential benefits not only as an emetic agent but also in chemotherapy.
Further in vivo animal and human studies to support this evidence is essentially needed.
Keywords : Cell cycle, Genotoxicity, Doxorubicin, Human lymphocyte, Sister chromatid exchange, Zingiber officinale rhizome
