㸦ู⣬ᵝᘧ㸴㸧(Attached Form 6)Ꮫ఩ㄽᩥࡢせ᪨㸦ㄽᩥࡢෆᐜࡢせ᪨㸧
Summary of the Dissertation (Summary of Dissertation Contents)ㄽ ᩥ 㢟 ┠Dissertation title
Anti-Blood Cancer Activities of Bioactive Compounds from Rice (Oryza sativa var. Koshihikari) and an
Invasive Weed (Andropogon virginicus)ᗈᓥ኱Ꮫ኱Ꮫ㝔ᅜ㝿༠ຊ◊✲⛉Graduate School for International Development and Cooperation,Hiroshima University༤ኈㄢ⛬ᚋᮇ
㛤Ⓨ⛉Ꮫᑓᨷ
Doctoral Program
Division of Development ScienceᏛ⏕␒ྕ
D190581Student ID No.
Ặྡ
LA HOANG ANHNameSeal
1. Background
Blood cancer (1.2 million cases per year) has been a serious human disease during a long history with ahigh mortality rate (58%). Therefore, this study was conducted to investigate promising candidates from plants forinhibiting blood cancer. Among plant sources, Adropogon virginicus is an invasive weed that distributes globally,
threatening agriculture and economics in many countries. Thus, research on pharmaceutical properties may lead tofurther strategies to take advantage of this serious invasive weed that was once thought to be of no use. On theother hand, rice (Oryza sativa) is an important food crop in the world, which has been recently being received
increasing attention for the research on medicinal purposes. In rice, momilactones are high valuable diterpene
lactones exhibiting multiple biological benefits. Based on these reasons, we aimed (1) to explore potential
phytochemicals and pharmaceutical properties of the invasive weed A. virginicus with focus on antioxidant,anti-skin aging, anti-diabetic, and anti-blood cancer properties and (2) to determine the potentials of momilactones
isolated from rice (O. sativa var. Koshihikari) for preventing blood cancer.
2. Structure of dissertationChapter 1. General introduction
Chapter 2. Pharmaceutical properties of an invasive weed Andropogon virginicus
Chapter 3. Cytotoxic activities of momilactones against leukemia, lymphoma, and multiple myeloma cell lines
Chapter 4. Cytotoxic mechanism of momilactones against acute promyelocytic leukemia and multiple myeloma
cell lines
Chapter 5. Effects of in vitro digestion on anti-blood cancer properties of momilactones
Chapter 6. General discussion
3. Materials and methods
Materials
A. virginicus’ aerial plant parts were extracted by Soxhlet extraction method, followed by liquid-liquid
phase extraction to obtain total crude (T-Anvi), hexane (H-Anvi), ethyl acetate, (E-Anvi), butanol (B-Anvi), andwater (H-Anvi) extracts.
Momilactones were isolated and purified from the laboratory of Plant Physiology and Biochemistry,
Hiroshima University, Japan (Quan et al., 2019b).
Biological activity
Antioxidant activities of samples were determined via antiradical (DPPH and ABTS), reducing
power,E-carotene bleaching assays (Quan et al., 2019).
Enzymatic assays including tyrosinase and ჴ-amylase inhibitory effects of A. virginicus’ extracts wereevaluated following the method presented by Quan et al. (2019).

Anticancer assays consisting of MTT, annexin V apoptosis, cell cycle, and western blotting wereconducted to screen the anticancer properties of momilactones. The corresponding cell lines for blood cancer wereincluded leukemia (HL60, Meg-01, and K562), lymphoma (Mino), and myeloma (KMS-11 and U266). Besides, anon-cancerous cell line namely MeT-5A was used in this study.
In vitro digestion model
The effects of in vitro digestion on the bioaccessibility and cytotoxic activities of momilactones against
blood cancer cell lines were investigated following the method described by Un et al. (2022).
Phytochemical analysis
The chemical analyses were conducted applying spectrophotometer, gas chromatography-mass
spectrometry (GC-MS), and liquid chromatography-electrospray ionization-tandem mass spectrometry(LC-ESI-MS/MS) methods.
4. Results and discussion
In Chapter 2, we indicate that the invasive weed A. virginicus may be a promising source of antioxidants,
anti-⍺-amylase, and anti-tyrosinase abilities, and cytotoxicity against chronic myeloid leukemia cell lines.
Besides, A. virginicus aerial parts are rich in flavonoids, palmitic acid, phytol, and γ-sitosterol, which may play avital role in the biological activities of the respective extracts.
From Chapter 3, we highlight that MB and MAB can inhibit various blood cancer cell lines including
leukemia, lymphoma, and multiple myeloma by inducing cell apoptosis. Notably, the cytotoxicity of MB andMAB is close to the well-known drugs of Doxorubicin in inhibiting Meg-01 and K562. Meanwhile thesecompounds are stronger than the widely applied medicines of Doxorubicin and Ibrutinib in suppressing HL-60 andU266, respectively. Whereas these compounds display an insignificant effect on non-cancerous cells.
In Chapter 4, MB and MAB at 5 µM promote acute promyelocytic leukemia (HL-60) and multiple
myeloma (U266) cell apoptosis by activating the phosphorylation of p-38 in the mitogen-activated protein kinase(MAPK) pathway and regulating the relevant proteins (BCL-2 and caspase-3) in the mitochondrial pathway.
Besides, these compounds may induce G2 phase arrest in HL-60 cell cycle through the activation of p-38 anddisruption of CDK1 and cyclin B1 complex. Meanwhile MB and MAB show insignificant effects on cell apoptosis
and cell cycle of non-cancerous cell line MeT-5A.
For Chapter 5, the finding shows that the bioaccessibility and cytotoxicity of momilactones significantly
reduce through the digestive stages including oral, gastric, and intestinal phases.
A general discussion is presented in Chapter 6. Particularly, this is the first study to highlight that A.
virginicus may be a promising source of antioxidant, anti-diabetic, anti-skin aging, and anti-blood cancer agents.
In addition, momilactones isolated from rice (O. sativa var. Koshihikari) husks can inhibit blood cancer celllines by regulating the proteins related to apoptosis and cell cycle pathways. However, cytotoxic activities ofmomilactones may be significantly decreased during digestion. Therefore, forthcoming studies should beconducted to improve the bioaccessibility of momilactones, followed by in vivo and clinical tests to confirm
their capacity to develop novel anti-blood cancer drugs. In another aspect, the combination of momilactones
from rice and isolated components from A. virginicus may be a potential approach for developing blood cancer
treatments, especially for patients complicated with other health problems such as oxidative stress and chronicdisorders.

備考

論文の要旨はＡ４判用紙を使用し，4,000字以内とする。ただし，英文の場合は1,500語以内とする。
Remark: The summary of the dissertation should be written on A4-size pages and should not exceed 4,000
Japanese characters. When written in English, it should not exceed 1,500 words.