Inhibitory Activity of Compounds Isolated from Ligustrum robustum (Roxb.) against HepG2 Liver Cancer Cells: Isocubein and 4-(2-Acetoxyethyl)phenol as Potential Candidates
Thu Nong Thi Anh, HOANG YEN DONG THI, PHƯƠNG THAO NGUYEN THI, , , , , , , Jul-2024, (Accepted/In press) In: Chemistry & Biodiversity, n/a, n/a, p. n/a
Overview
Abstract:
Many herbal species in the genus Ligustrum have been shown to contain compounds with anti-cancer
biological activity. This study aimed to isolate some compounds from the leaves of Ligustrum
robustum (Roxb.) Blume (L. robustum) and evaluate their effects against liver cancer cells. As a result,
seven previously reported compounds (1-7) were isolated, including four lignans (1–4) and three
phenolic derivatives (5–7). The structures of these compounds were determined using spectroscopic
methods and comparison with reported data. All isolates were assessed for their inhibitory effects on
HepG2 liver cancer cells. Screening results revealed that two compounds, isocubein (3) and 4-(2-
acetoxyethyl)phenol (7), exhibited strong inhibitory activity against cell proliferation, with IC50 values
of 3.1±0.9 and 4.5±14 µM, respectively. Further analyses demonstrated that both compounds could
suppress the formation and development of 3D tumorspheres in terms of quantity and size.
Additionally, isocubein (3) and 4-(2-acetoxyethyl)phenol (7) exhibited the ability to inhibit the
10.1002/cbdv.202401065
Accepted Manuscript
Chemistry & Biodiversity
This article is protected by copyright. All rights reserved.
16121880, ja, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/cbdv.202401065 by Uppsala University Library, Wiley Online Library on [16/07/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
migration of HepG2 cells. This study represents the first report on the inhibitory activity against HepG2
liver cancer cells of extracts and isolated compounds from L. robustum, providing valuable information
for future research aiming to develop products for liver cancer treatment.
Key words: HepG2 cancer cells, migraiton, Ligustrum robustum, isocubein, 4-(2-
acetoxyethyl)phenol.
Introduction
Hepatocellular carcinoma (HCC) is a prevalent disease worldwide, ranking fourth in cancer-related
mortalities with 800,000 deaths annually.[1] It is estimated that there will be over 1 million new cases
in 2025, with HCC constituting 90% of primary liver cancer cases.[2] Chronic liver diseases, such as
hepatitis B and C virus infections, cirrhosis, and non-alcoholic fatty liver disease, are major
contributors to liver cancer.[3] Despite advancements in imaging diagnostics and biomarker testing,
liver cancer is often diagnosed at advanced stages, limiting treatment options. At this stage, systemic
therapies such as chemotherapy, immunotherapy, and targeted therapies are prioritized to prolong
patient survival; however, these therapies are associated with considerable side effects, limited
response rates, and high recurrence rates.[4-6] The prognosis for patients with advanced liver cancer is
poor, necessitating the development of novel therapeutic approaches to address current treatment
limitations.[7] Research on cancer treatment using compounds derived from herbs has emerged as a
promising direction, clinically proven to effectively kill cancer cells with fewer adverse effects and
reduced drug resistance.[8] Some natural compounds used to support liver cancer treatment include
curcumin, resveratrol, silibinin, berberine, quercetin, tanshinone II-A, and celastrol.[9] The genus
Ligustrum, belonging to the Oleaceae family, is commonly used in traditional chinese medicine. It
comprises 80 species native to Europe, North Africa, Asia, and Australia, consisting of small to
medium-sized erect shrubs. Several Ligustrum species have demonstrated the ability to eliminate
various cancer cells. L. robustum exhibits cytotoxicity against HeLa (Cervical cancer), MCF-7 (Breast
cancer), PC-3 (Prostate cancer), SMMC-7721 (Hepatocellular carcinoma), and SW480 (colorectal
cancer) cancer cell lines.[10] Nanosilver complex synthesized from L. ovalifolium demonstrates
anticancer activity against ovarian cancer cell lines A2780 and A2780-Cis.[11] Particularly, extracts
10.1002/cbdv.202401065
biological activity. This study aimed to isolate some compounds from the leaves of Ligustrum
robustum (Roxb.) Blume (L. robustum) and evaluate their effects against liver cancer cells. As a result,
seven previously reported compounds (1-7) were isolated, including four lignans (1–4) and three
phenolic derivatives (5–7). The structures of these compounds were determined using spectroscopic
methods and comparison with reported data. All isolates were assessed for their inhibitory effects on
HepG2 liver cancer cells. Screening results revealed that two compounds, isocubein (3) and 4-(2-
acetoxyethyl)phenol (7), exhibited strong inhibitory activity against cell proliferation, with IC50 values
of 3.1±0.9 and 4.5±14 µM, respectively. Further analyses demonstrated that both compounds could
suppress the formation and development of 3D tumorspheres in terms of quantity and size.
Additionally, isocubein (3) and 4-(2-acetoxyethyl)phenol (7) exhibited the ability to inhibit the
10.1002/cbdv.202401065
Accepted Manuscript
Chemistry & Biodiversity
This article is protected by copyright. All rights reserved.
16121880, ja, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/cbdv.202401065 by Uppsala University Library, Wiley Online Library on [16/07/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
migration of HepG2 cells. This study represents the first report on the inhibitory activity against HepG2
liver cancer cells of extracts and isolated compounds from L. robustum, providing valuable information
for future research aiming to develop products for liver cancer treatment.
Key words: HepG2 cancer cells, migraiton, Ligustrum robustum, isocubein, 4-(2-
acetoxyethyl)phenol.
Introduction
Hepatocellular carcinoma (HCC) is a prevalent disease worldwide, ranking fourth in cancer-related
mortalities with 800,000 deaths annually.[1] It is estimated that there will be over 1 million new cases
in 2025, with HCC constituting 90% of primary liver cancer cases.[2] Chronic liver diseases, such as
hepatitis B and C virus infections, cirrhosis, and non-alcoholic fatty liver disease, are major
contributors to liver cancer.[3] Despite advancements in imaging diagnostics and biomarker testing,
liver cancer is often diagnosed at advanced stages, limiting treatment options. At this stage, systemic
therapies such as chemotherapy, immunotherapy, and targeted therapies are prioritized to prolong
patient survival; however, these therapies are associated with considerable side effects, limited
response rates, and high recurrence rates.[4-6] The prognosis for patients with advanced liver cancer is
poor, necessitating the development of novel therapeutic approaches to address current treatment
limitations.[7] Research on cancer treatment using compounds derived from herbs has emerged as a
promising direction, clinically proven to effectively kill cancer cells with fewer adverse effects and
reduced drug resistance.[8] Some natural compounds used to support liver cancer treatment include
curcumin, resveratrol, silibinin, berberine, quercetin, tanshinone II-A, and celastrol.[9] The genus
Ligustrum, belonging to the Oleaceae family, is commonly used in traditional chinese medicine. It
comprises 80 species native to Europe, North Africa, Asia, and Australia, consisting of small to
medium-sized erect shrubs. Several Ligustrum species have demonstrated the ability to eliminate
various cancer cells. L. robustum exhibits cytotoxicity against HeLa (Cervical cancer), MCF-7 (Breast
cancer), PC-3 (Prostate cancer), SMMC-7721 (Hepatocellular carcinoma), and SW480 (colorectal
cancer) cancer cell lines.[10] Nanosilver complex synthesized from L. ovalifolium demonstrates
anticancer activity against ovarian cancer cell lines A2780 and A2780-Cis.[11] Particularly, extracts
10.1002/cbdv.202401065
Keyword(s): HepG2 cancer cells, migraiton, Ligustrum robustum, isocubein, 4-(2- acetoxyethyl)phenol.
| Article number | n/a |
| Journal | Chemistry & Biodiversity |
| Volume | n/a |
| Issue number | n/a |
| Publication status | Accepted/In press - Jul-2024 |
| ISBN | 1612-1880 |