Wortel 1

ABSTRACT Overwhelming evidence indicates that consumption of fruits and

vegetables with antioxidant properties correlates with reduced risk for cancers,
including leukemia. Carrots contain benecial agents, such as b-carotene and
polyacetylenes, which could be effective in the treatment of leukemia. This study
investigated the effect of carrot juice extracts on myeloid and lymphoid leukemia
cell lines together with normal hematopoietic stem cells. Leukemia cell lines and
nontumor control cells were treated with carrot juice extracts for up to 72 hours in
vitro. Induction of apoptosis was investigated by using annexin V/propidium iodide
staining followed by ow cytometric analysis, and results were conrmed by using
40-6diamidino-2-phenylindole morphology. Effects on cellular proliferation were
investigated via cell cycle analysis and cell counts. Treatment of leukemia cell lines
with carrot juice extract induced apoptosis and inhibited progression through the
cell cycle. Lymphoid cell lines were affected to a greater extent than were myeloid
cell lines, and normal hematopoietic stem cells were less sensitive than most cell
lines. This study has shown that extracts from carrots can induce apoptosis and
cause cell cycle arrest in leukemia cell lines. The ndings suggest that carrots may
be an excellent source of bioactive chemicals for the treatment of leukemia.
Wortel 2
Abstract: New therapies for leukaemia are urgently needed. Carrots have been
suggested as a potential treatment for leukaemia in traditional medicine and have
previously been studied in other contexts as potential sources of anticancer agents.
Indicating that carrots may contain bioactive compounds, which may show potential
in leukaemia therapies. This study investigated the effects of ve fractions from
carrot juice extract (CJE) on human lymphoid leukaemia cell lines, together with ve
puried bioactive compounds found in Daucus carota L, including: three
polyacetylenes (falcarinol, falcarindiol and falcarindiol-3-acetate) and two
carotenoids (beta-carotene and lutein). Their effects on induction of apoptosis using
Annexin V/PI and Caspase 3 activity assays analysed via ow cytometry and
inhibition of cellular proliferation using Cell Titer Glo assay and cell cycle analysis
were investigated. Treatment of all three lymphoid leukaemia cell lines with the
fraction from carrot extracts which contained polyacetylenes and carotenoids was
signicantly more cytotoxic than the 4 other fractions. Treatments with puried
polyacetylenes also induced apoptosis in a dose and time responsive manner.
Moreover, falcarinol and falcarindiol-3-acetate isolated from Daucus carota L were
more cytotoxic than falcarindiol. In contrast, the carotenoids showed no signicant
effect on either apoptosis or cell proliferation in any of the cells investigated. This
suggests that polyacetylenes rather than beta-carotene or lutein are the bioactive
components found in Daucus carota L and could be useful in the development of
new leukemic therapies. Here, for the rst time, the cytotoxic effects of
polyacetylenes have been shown to be exerted via induction of apoptosis and arrest
of cell cycle.

Orange 1
Abstract Background Hesperidin, a avanone present in citrus fruits, has been
identied as a potent anticancer agent because of its proapoptotic and
antiproliferative characteristics in some tumor cells. However, the precise
mechanisms of action are not entirely understood. Aim The main purpose of this
study is to investigate the involvement of peroxisome proliferator-activated
receptorgamma (PPARc) in hesperidins anticancer actions in human pre-B NALM-6
cells, which expresses wild-type p53.
Methods The effects of hesperidin on cell-cycle distribution, proliferation, and
caspase-mediated apoptosis were examined in NALM-6 cells in the presence or
absence of GW9662. The expression of peroxisome proliferator-activated receptorgamma (PPARc), p53, phospho-IjB, Bcl-2, Bax, and XIAP proteins were focused on
using the immunoblotting assay. The transcriptional activities of PPARc and nuclear
factor-kappaB (NF-jB) were analyzed by the transcription factor assay kits. The
expression of PPARc and p53 was analyzed using the RT-PCR method. Results
Hesperidin induced the expression and transcriptional activity of PPARc and
promoted p53 accumulation and downregulated constitutive NF-jB activity in a
PPARc-dependent and PPARc-independent manner. The
growth-inhibitory effect of hesperidin was partially reduced when the cells
preincubated with PPARc antagonist prior to the exposure to hesperidin. Conclusions
The ndings of this study clearly demonstrate that hesperidin-mediated
proapoptotic and antiproliferative actions are regulated via both PPARc-dependent
and PPARc-independent pathways in NALM-6 cells. These data provide the rst
evidence that hesperidin could be developed as an agent against hematopoietic
malignancies.
Orange 2
Abstract. Citrus fruits have been used as edible fruits and a traditional medicine
since ancient times. In particular, the peels of immature citrus fruits are frequently
prescribed in concert with other support herbs for many types of disease including
cancer. We investigated the anti-proliferative activity of the peels of Citrus
aurantium L. along with their effects on apoptosis. We prepared crude methanol
extracts of the peels of Citrus aurantium L. (CMEs) and performed experiments
using U937 human leukemia cells. The growth of U937 cells was inhibited by CME
treatment in a dose dependent manner, and CME induced caspase-dependent
apoptosis. CME inhibited the expression of XIAP and Bcl-xL which are anti-apoptotic

proteins. CME inhibited Akt activity in a dose-dependent manner. The apoptotic

activity of CME was signicantly attenuated by Akt augmentation. In conclusion, this
study suggested that CME should induce caspase-dependent apoptosis at least in
part through Akt inhibition, providing evidence that CMEs have anticancer activity
on human leukemia cells.

Potensi Teknologi Nanoenkapsulasi Kombinasi Ekstrak Wortel (Daucus

carota) dan Jeruk (Citrus aurantium L.) sebagai Modalitas Terapi
Komprehensif dalam Penatalaksanaan Leukemia
Latar belakang
Konsumsi berbagai buah dan sayur yang kaya akan antioksidan telah dibuktikan
dalam berbagai penelitian dapat menurunkan risiko terkena kanker, seperti
leukemia. Salah satu buah dan sayur tersebut adalah wortel dan jeruk. Wortel
(Daucus carota) dengan kandungan bioaktif betakaroten dan poliasetilens
(falcarinol, falcarindiol dan falcarindiol-3-asetat) dan jeruk (Citrus aurantium L.)
dengan hesperidin diperkirakan mampu menjadi terapi adjuvant dari leukemia
dengan cara meningkatkan apoptosis sel kanker dan menginduksi ekspresi
peroxisome proliferator-activated receptor gamma (PPAR) yang mampu memicu
ekspresi gen p53 sebagai supresor terhadap sel kanker.
Terapi leukemia saat ini kebanyakan menimbulkan efek samping bagi pasien seperti
penurunan jumlah sel darah (eritrositopenia dan neutropenia). Hal ini akan
meningkatkan risiko terjadinya anemia dan peningkatan risiko akan infeksi, mudah
merasa lelah, depresi, keringat berlebih atau sering merasakan sensasi demam.
Terapi adjuvant yang bersifat alami diperkirakan memiliki efek samping yang lebih
rendah dan memiliki efek tambahan yang bersifat protektif dan terapeutik terhadap
perkembangan kanker.
Tujuan
Untuk menunjukkan potensi kombinasi ekstrak wortel (Daucus carota) dan jeruk
(Citrus aurantium L.) sebagai terapi neoadjuvant dalam menangani leukemia.
Metode
Studi literatur dengan menggunakan data-data dari berbagai referensi yang relevan
untuk kemudian dianalisis dan disimpulkan menjadi suatu gagasan alternatif yang
lebih baik dari terapi sebelumnya.

Kerangka Teori
Leukemia adalah keadaan di mana terdapat proliferasi sel leukosit yang abnormal,
ganas, sering disertai bentuk leukosit yang tidak normal dengan jumlah yang
berlebihan dan dapat menyebabkan kegagalan pada sumsum tulang. Leukemia
terjadi akibat gangguan dari proses pematangan dari sel punca menjadi sel darah
putih dan menghasilkan suatu perubahan menjadi keganasan. Perubahan tersebut
melibatkan perubahan susunan kromosom terutama translokasi kromosom.
Sehingga siklus sel darah putih terus membelah menjadi tidak terkendali.
Kandungan beta-karoten pada wortel (Daucus carota) mampu meningkatkan
apoptosis dari sel darah putih dan menekan siklus sel di fase G0/G1. Selain itu,
poliasetilens pada wortel juga bersifat sitotoksik terhadap kumpulan sel leukemia,
myeloma, dan limfoma berdasarkan pemeriksaan annexin V/propidium iodide.
Jeruk dengan hesperidine berdasarkan penelitian mampu menginduksi ekspresi dan
aktivitas transkripsi dari PPAR gamma pada sel leukemia. Induksi ini menyebabkan
akumulasi p53 sebagai gen supresor terhadap kanker sehingga tubuh mulai
membangun proteksi terhadap antikanker.

Hasil dan Pembahasan

Dari studi sebelumnya diketahui bahwa pemanfaatan ekstrak jus wortel (Daucus
carota)